The long term objective of the proposed research is to learn what controls whether injuries heal with scarring/fibrosis versus full regeneration of los structures. The human health burden of fibrosis and scarring is enormous and affects every tissue from heart (lost heart function after a myocardial infarction) to lung (idiopathic lung fibrosis). Enhancing regeneration could prevent for example the almost universal recurrence of chronic wounds in the exact location where they previously appeared. We use the Wound Induced Hair Neogenesis (WIHN) model system where in the center of excisional wounds in mice a variable amount of regeneration occurs and de novo hair follicles form in a recapitulation of embryogenesis. The goal of this grant is to understand the factors which control the frequency of regeneration. We will directly test the mechanism and the ability for candidate molecules which enhance regeneration in mice to do so in human subjects. The results of this grant promise to help define new treatments and diagnostics to enhance regeneration and wound healing.